Year: 2017
Type: preprint
Abstract: We hypothesized that transcription factors (TFs) recognize DNA shape without nucleotide sequence recognition. Motivating an independent role for shape, many TF binding sites lack a sequence-motif, DNA shape adds specificity to sequence-motifs, and different sequences can encode similar shapes. We therefore asked if binding sites of a TF are enriched for specific patterns of DNA shape-features, e.g., helical twist. We developed ShapeMF, which discovers these shape-motifs de novo without taking sequence information into account. We find that most TFs assayed in ENCODE have shape-motifs and bind regulatory regions recognizing shape-motifs in the absence of sequence-motifs. When shape- and sequence-recognition co-occur, the two types of motifs can be overlapping, flanking, or separated by consistent spacing. Shape-motifs are prevalent in regions co-bound by multiple TFs. Finally, TFs with identical sequence motifs have different shape-motifs, explaining their binding at distinct locations. These results establish shape-motifs as drivers of TF-DNA recognition complementary to sequence-motifs.
DOI: 10.1101/143677
Institutions: Gladstone Institutes, University of California, San Francisco
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2619085019